Composition:
Utilisé dans le traitement:
Examiné médicalement par Militian Inessa Mesropovna, Pharmacie Dernière mise à jour le 24.03.2022
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Tenton a des propriétés analgésiques et anti-inflammatoires non stéroïdiennes.
Il est indiqué pour les conditions suivantes:
- stades actifs de la polyarthrite rhumatoïde, de l'arthrose, de la spondylarthrite ankylosante, de la maladie articulaire dégénérative de la hanche, des troubles musculo-squelettiques aigus, de la goutte et du lumbago.
- inflammation, douleur et œdème suite à des procédures orthopédiques.
- traitement de la douleur et des symptômes associés de la dysménorrhée primaire.
Étant donné que Tenton n'est pas un simple analgésique, son utilisation doit être limitée aux conditions ci-dessus.
La suspension buvable de Tenton est indiquée pour:
- Polyarthrite rhumatoïde modérée à sévère, y compris les poussées aiguës de maladies chroniques
- Spondylarthrite ankylosante modérée à sévère
- Arthrose modérée à sévère
- Épaule douloureuse aiguë (bursite et / ou tendinite)
- Arthrite goutteuse aiguë
Agent anti-inflammatoire non stéroïdien indiqué pour les stades actifs de la polyarthrite rhumatoïde, de l'arthrose, de la spondylarthrite ankylosante, des troubles musculo-squelettiques aigus, des maladies articulaires dégénératives de la hanche, des douleurs à faible dos et de la polyarthrite goutteuse aiguë.
Également indiqué dans l'inflammation, la douleur et l'œdème après les procédures orthopédiques; et le traitement de la douleur et des symptômes associés de la dysménorrhée primaire.
Posologie
La posologie doit être soigneusement ajustée en fonction des besoins de chaque patient.
Pour réduire la possibilité de troubles gastro-intestinaux, les gélules de Tenton doivent toujours être prises avec de la nourriture, du lait ou un antiacide et, dans les conditions chroniques, commencer le traitement avec une faible dose, augmentant au besoin.
Adultes: La plage de dosage oral recommandée est de 50 à 200 mg par jour.
Polyarthrite rhumatoïde aiguë: Initialement 25 mg deux ou trois fois par jour.
Troubles rhumatismaux chroniques: 25 mg deux ou trois fois par jour. (Si la réponse est inadéquate, augmentez progressivement de 25 mg. Une réponse adéquate est généralement obtenue avec pas plus de 150 mg par jour, rarement plus de 200 mg par jour).
Éruption soudaine de la maladie chronique : Augmenter si nécessaire, de 25 mg par jour jusqu'à ce qu'une réponse satisfaisante soit obtenue, ou une posologie de 150 à 200 mg par jour est atteinte. (Si cela provoque des effets indésirables, il doit être réduit à un niveau tolérable pendant deux ou trois jours, puis soigneusement augmenté, comme toléré).
Affections musculo-squelettiques aiguës: Initialement 50 mg deux ou trois fois par jour, selon la gravité pendant 10 à 14 jours. Normalement 150 mg par jour, rarement 200 mg par jour.
Lumbago : 50 mg deux ou trois fois par jour, selon la gravité. La durée du traitement ne dépasse normalement pas cinq jours, mais peut être poursuivie jusqu'à 10 jours.
Goutte: Attaque aiguë: 50 mg trois ou quatre fois par jour jusqu'à ce que les symptômes disparaissent.
Procédures orthopédiques suivantes: Normalement, 100 à 150 mg par jour en doses divisées jusqu'à ce que les symptômes disparaissent.
Considérations supplémentaires: Dans les conditions où les patients ont besoin d'une posologie de 150 à 200 mg par jour, il est souvent possible de le réduire progressivement à un niveau d'entretien de 75 à 100 mg par jour. Chez les patients souffrant de douleurs nocturnes persistantes et / ou de raideurs matinales, une dose allant jusqu'à 100 mg au coucher peut être utile pour soulager. Il est rarement nécessaire de dépasser une dose de 200 mg par jour.
Personnes âgées: Les personnes âgées courent un risque accru de conséquences graves des effets indésirables. Si un AINS est jugé nécessaire, la dose efficace la plus faible doit être utilisée et pour la durée la plus courte possible. Le patient doit être surveillé régulièrement pour les saignements gastro-intestinaux pendant le traitement par AINS.
Enfants: La sécurité d'utilisation chez les enfants n'a pas été établie.
Les effets indésirables peuvent être minimisés en utilisant la dose efficace la plus faible pendant la durée la plus courte nécessaire pour contrôler les symptômes.
Mode d'administration
Pour administration orale.
À prendre de préférence avec ou après la nourriture.
Instructions générales de dosage
Considérez attentivement les avantages et les risques potentiels de Tenton et d'autres options de traitement avant de décider d'utiliser Tenton. Utilisez la posologie efficace la plus faible pour la durée la plus courte compatible avec les objectifs de traitement individuels des patients.
Après avoir observé la réponse au traitement initial par l'indométhacine, la dose et la fréquence doivent être ajustées en fonction des besoins d'un patient individuel.
Les effets indésirables semblent généralement être en corrélation avec la dose d'indométhacine. Par conséquent, tous les efforts doivent être faits pour déterminer la posologie efficace la plus faible pour chaque patient.
Recommandations posologiques pour les étapes actives des éléments suivants:
Arthrite rhumatoïde modérée à sévère, y compris les poussées aiguës de maladies chroniques; Spondylarthrite ankylosante modérée à sévère; Et une arthrose modérée à sévère
Tenton 25 mg (5 ml) deux fois par jour ou trois fois par jour. Si cela est bien toléré, augmenter la posologie quotidienne de 25 mg (5 ml) ou par 50 mg (10 ml) si requis par les symptômes persistants, à intervalles hebdomadaires jusqu'à l'obtention d'une réponse satisfaisante ou jusqu'à une dose quotidienne totale de 150 à 200 mg (30 - 40 ml) est atteint. Les doses supérieures à cette quantité n'augmentent généralement pas l'efficacité du médicament.
Chez les patients qui souffrent de douleurs nocturnes persistantes et / ou de raideurs matinales, l'administration d'une grande partie, jusqu'à un maximum de 100 mg (20 ml), de la dose quotidienne totale au coucher peut être utile pour soulager. La dose quotidienne totale ne doit pas dépasser 200 mg (40 ml). Dans les poussées aiguës de polyarthrite rhumatoïde chronique, il peut être nécessaire d'augmenter la posologie de 25 mg (5 ml) ou, si nécessaire, de 50 mg (10 ml) par jour. Si des effets indésirables mineurs se développent à mesure que la posologie augmente, réduisez rapidement la posologie à une dose tolérée et observez le patient de près.
En cas d'effets indésirables graves, arrêtez le médicament. Une fois la phase aiguë de la maladie sous contrôle, une tentative de réduction de la dose quotidienne doit être effectuée à plusieurs reprises jusqu'à ce que le patient reçoive la plus petite dose efficace ou que le médicament soit arrêté.
Des instructions et des observations minutieuses à l'intention de chaque patient sont essentielles à la prévention des effets indésirables graves, irréversibles, y compris mortels.
Comme les années qui avancent semblent augmenter la possibilité d'effets indésirables, Tenton doit être utilisé avec plus de soins chez les personnes âgées.
Épaule douloureuse aiguë (bursite et / ou tendinite)
Tenton 75-150 mg (15-30 ml) par jour en 3 ou 4 doses divisées.
Le médicament doit être arrêté après que les signes et symptômes de l'inflammation ont été contrôlés pendant plusieurs jours. Le cours de thérapie habituel est de 7 à 14 jours.
Arthrite goutteuse aiguë
Tenton 50 mg (10 ml) trois fois par jour jusqu'à ce que la douleur soit tolérable. La dose doit ensuite être rapidement réduite pour terminer l'arrêt du médicament. Un soulagement définitif de la douleur a été signalé dans les 2 à 4 heures.
La sensibilité et la chaleur diminuent généralement en 24 à 36 heures et l'enflure disparaît progressivement en 3 à 5 jours.
La posologie de 'Tenton' doit être soigneusement ajustée en fonction des besoins de chaque patient.
Afin de réduire les risques de troubles gastro-intestinaux, Les capsules «Tenton» doivent toujours être prises avec de la nourriture ou un antiacide.
Dans les maladies chroniques, le démarrage d'un traitement à faible dose, l'augmentation progressive si nécessaire et la poursuite d'un essai de thérapie pendant une période adéquate (dans certains cas, jusqu'à un mois) donneront les meilleurs résultats avec un minimum de réactions indésirables. La dose posologique orale recommandée est de 50 mg à 200 mg par jour en doses divisées. Posologie pédiatrique non établie.
Posologie en dysménorrhée: Jusqu'à 75 mg par jour, en commençant par l'apparition de crampes ou de saignements, et en continuant aussi longtemps que les symptômes durent habituellement.
Posologie dans l'arthrite goutteuse aiguë: 150 mg à 200 mg par jour en doses divisées jusqu'à ce que tous les symptômes et signes disparaissent.
Utiliser chez les personnes âgées: 'Tenton' doit être utilisé avec un soin particulier chez les patients plus âgés qui sont plus sujets aux effets indésirables.
- Les AINS sont contre-indiqués chez les patients qui ont déjà montré des réactions d'hypersensibilité (eg asthme, rhinite, œdème de Quincke ou urticaire) en réponse à l'ibuprofène, à l'aspirine, ou d'autres anti-inflammatoires non stéroïdiens.
- Hypersensibilité à Tenton ou à l'un des excipients.
- Insuffisance cardiaque sévère, insuffisance hépatique et insuffisance rénale.
- Ne pas utiliser chez les patients atteints de polypes nasaux
- Au cours du dernier trimestre de la grossesse.
- La sécurité des enfants n'a pas été établie.
- Actif ou antécédents d'ulcère / hémorragie gastro-duodénale récurrente (deux épisodes distincts ou plus d'ulcération ou de saignement prouvés).
- Antécédents de saignement ou de perforation gastro-intestinale, liés à un traitement antérieur par les AINS.
Tenton est contre-indiqué chez les patients suivants:
- Hypersensibilité connue (par ex., réactions anaphylactiques et réactions cutanées graves) à l'indométhacine ou à tout composant du produit médicamenteux
- Antécédents d'asthme, d'urticaire ou d'autres réactions de type allergique après la prise d'aspirine ou d'autres AINS. Des réactions anaphylactiques sévères, parfois mortelles, aux AINS ont été rapportées chez ces patients
- Dans le cadre de la chirurgie de pontage aortocoronarien (CABG)
Antécédents d'ulcère gastro-duodénal ou d'ulcère gastro-duodénal actif; une histoire récurrente de lésions gastro-intestinales; chez les patients atteints de polypes nasaux associés à un œdème angioneurotique, qui présentent une sensibilité à l'indométhacine ou à l'un des ingrédients de ce produit, ou qui ont subi des attaques asthmatiques aiguës, urticaire ou rhinite à la suite d'un traitement à l'aspirine ou à d'autres anti-inflammatoires non stéroïdiens.
La sécurité d'utilisation chez les enfants n'a pas été établie.
<'Grossesse et allaitement').
- The use of Tenton capsules with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors, should be avoided
- Cardiovascular and cerebrovascular effects
Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.
Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).).
Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.
- Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
- Respiratory disorders:
Caution is required if administered to patients suffering from, or with a previous history of, bronchial asthma since NSAIDs have been reported to precipitate bronchospasm in such patients.
- Caution is advised in patients with pre-existing sigmoid lesions (such as diverticulum or carcinoma) (or the development of these conditions) as
Tenton can aggravate these conditions.
- Gastrointestinal bleeding, ulceration and perforation:
GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or previous history of serious GI events.
When GI bleeding or ulceration occurs in patients receiving Tenton, the treatment should be withdrawn.
The risk of GI bleeding, ulceration or perforation is higher with increasing
NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation , and in the elderly.).
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated.
- SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
- Impaired female fertility:
The use of Tenton may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of Tenton should be considered.
- Tenton should be used with caution in patients with coagulation defects as Tenton can inhibit platelet aggregation. This effect may be exaggerated in patients with underlying haemostatic defects. Inhibition of platelet aggregation usually disappears within 24 hours of discontinuing Tenton.
- Caution is required in post-operative patients as bleeding time is prolonged (but within normal range) in normal adults.
- During prolonged therapy, periodic ophthalmic examinations are recommended, as corneal deposits and retinal disturbances have been reported. In patients with rheumatoid arthritis, eye changes may occur which may be related to the underlying disease or to the therapy.
Therefore, in chronic rheumatoid disease, ophthalmological examinations are periodic intervals are recommended. Therapy should be discontinued if eye changes are observed.
- Patients should be periodically observed to allow early detection of any unwanted effects on peripheral blood (anaemia), liver function , or gastrointestinal tract especially during prolonged therapy.
- Medication Overuse Headache (MOH):
After long term treatment with analgesics, headache may develop or aggravate. Headache caused by overuse of analgesics (MOH - medication-overuse headache) should be suspected in patients who have frequent or daily headaches despite (or because of) regular use of analgesics. Patients with medication overuse headache should not be treated by increasing the dose. In such cases the use of analgesics should be discontinued in consultation with a doctor.
- Avoid concomitant use of two or more NSAIDs.
- Dermatological:
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Tenton capsules should be discontinued at the first appearance of skin rash, mucosal lesions, and any other sign of hypersensitivity.
- Increases in plasma potassium concentration, including hyperkalaemia have been reported, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninaemic-hypoaldosteronism state.
WARNINGS
Included as part of the PRECAUTIONS section.
PRECAUTIONS
Cardiovascular Thrombotic Events
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI) and stroke, which can be fatal. Based on available data, it is unclear that the risk for CV thrombotic events is similar for all NSAIDs. The relative increase in serious CV thrombotic events over baseline conferred by NSAID use appears to be similar in those with and without known CV disease or risk factors for CV disease. However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses.
To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible. Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID, such as indomethacin, increases the risk of serious gastrointestinal (GI) events.
Status Post Coronary Artery Bypass Graft (CABG) Surgery
Two large, controlled clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10–14 days following CABG surgery found an increased incidence of myocardial infarction and stroke. NSAIDs are contraindicated in the setting of CABG.
Post-MI Patients
Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfarction, CV-related death, and allcause mortality beginning in the first week of treatment. In this same cohort, the incidence of death in the first year post-MI was 20 per 100 person years in NSAID-treated patients compared to 12 per 100 person years in non-NSAID exposed patients. Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up.
Avoid the use of Tenton in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Tenton is used in patients with a recent MI, monitor patients for signs of cardiac ischemia.
Gastrointestinal Bleeding, Ulceration, And Perforation
NSAIDs, including indomethacin, cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients who develop a serious upper GI adverse event on NSAID therapy is symptomatic. Upper GI ulcers, gross bleeding, or perforation caused by NSAIDs occurred in approximately 1% of patients treated for 3-6 months, and in about 2%-4% of patients treated for one year. However, even short-term NSAID therapy is not without risk.
Risk Factors For GI Bleeding, Ulceration, And Perforation
Patients with a prior history of peptic ulcer disease and/or GI bleeding who used NSAIDs had a greater than 10-fold increased risk for developing a GI bleed compared to patients without these risk factors. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors (SSRIs); smoking; use of alcohol; older age; and poor general health status. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. Additionally, patients with advanced liver disease and/or coagulopathy are at increased risk for GI bleeding.
Strategies To Minimize The GI Risks In NSAID-treated patients:
- Use the lowest effective dosage for the shortest possible duration.
- Avoid administration of more than one NSAID at a time.
- Avoid use in patients at higher risk unless benefits are expected to outweigh the increased risk of bleeding. For such patients, as well as those with active GI bleeding, consider alternate therapies other than NSAIDs.
- Remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy.
- If a serious GI adverse event is suspected, promptly initiate evaluation and treatment, and discontinue Tenton until a serious GI adverse event is ruled out.
- In the setting of concomitant use of low-dose aspirin for cardiac prophylaxis, monitor patients more closely for evidence of GI bleeding.
Hepatotoxicity
Elevations of ALT or AST (three or more times the upper limit of normal [ULN]) have been reported in approximately 1% of NSAID-treated patients in clinical trials. In addition, rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure have been reported.
Elevations of ALT or AST (less than three times ULN) may occur in up to 15% of patients treated with NSAIDs including indomethacin.
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), discontinue Tenton immediately, and perform a clinical evaluation of the patient.
Hypertension
NSAIDs, including Tenton, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE) inhibitors, thiazide diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs.
Monitor blood pressure (BP) during the initiation of NSAID treatment and throughout the course of therapy.
Heart Failure And Edema
The Coxib and traditional NSAID Trialists' Collaboration meta-analysis of randomized controlled trials demonstrated an approximately two-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared to placebo-treated patients. In a Danish National Registry study of patients with heart failure, NSAID use increased the risk of MI, hospitalization for heart failure, and death.
Additionally, fluid retention and edema have been observed in some patients treated with NSAIDs. Use of indomethacin may blunt the CV effects of several therapeutic agents used to treat these medical conditions (e.g., diuretics, ACE inhibitors, or angiotensin receptor blockers [ARBs]).
Avoid the use of Tenton in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If Tenton is used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Renal Toxicity And Hyperkalemia
Renal Toxicity
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.
Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID may cause a dosedependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
No information is available from controlled clinical studies regarding the use of Tenton in patients with advanced renal disease. The renal effects of Tenton may hasten the progression of renal dysfunction in patients with preexisting renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating Tenton. Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use of Tenton. Avoid the use of Tenton in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. If Tenton is used in patients with advanced renal disease, monitor patients for signs of worsening renal function.
It has been reported that the addition of the potassium-sparing diuretic, triamterene, to a maintenance schedule of indomethacin resulted in reversible acute renal failure in two of four healthy volunteers. Â Indomethacin and triamterene should not be administered together.
Hyperkalemia
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state.
Both Indomethacin and potassium-sparing diuretics may be associated with increased serum potassium levels. The potential effects of indomethacin and potassium-sparing diuretics on potassium levels and renal function should be considered when these agents are administered concurrently.
Anaphylactic Reactions
Indomethacin has been associated with anaphylactic reactions in patients with and without known hypersensitivity to indomethacin and in patients with aspirin-sensitive asthma.
Seek emergency help if an anaphylactic reaction occurs.
Exacerbation Of Asthma Related To Aspirin Sensitivity
A subpopulation of patients with asthma may have aspirin-sensitive asthma which may include chronic rhinosinusitis complicated by nasal polyps; severe, potentially fatal bronchospasm; and/or intolerance to aspirin and other NSAIDs. Because cross-reactivity between aspirin and other NSAIDs has been reported in such aspirin-sensitive patients, Tenton is contraindicated in patients with this form of aspirin sensitivity. When Tenton is used in patients with preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of asthma.
Serious Skin Reactions
NSAIDs, including indomethacin, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions, and to discontinue the use of Tenton at the first appearance of skin rash or any other sign of hypersensitivity. Tenton is contraindicated in patients with previous serious skin reactions to NSAIDs.
Premature Closure Of Fetal Ductus Arteriosus
Indomethacin may cause premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Tenton, in pregnant women starting at 30 weeks of gestation (third trimester).
Hematologic Toxicity
Anemia has occurred in NSAID-treated patients. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis. If a patient treated with Tenton has any signs or symptoms of anemia, monitor hemoglobin or hematocrit.
NSAIDs, including Tenton, may increase the risk of bleeding events. Co-morbid conditions, such as coagulation disorders, or concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may increase this risk. Monitor these patients for signs of bleeding.
Masking Of Inflammation And Fever
The pharmacological activity of Tenton in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.
Laboratory Monitoring
Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider monitoring patients on long-term NSAID treatment with a CBC and a chemistry profile periodically.
Central Nervous System Effects
Tenton may aggravate depression or other psychiatric disturbances, epilepsy, and parkinsonism, and should be used with considerable caution in patients with these conditions. Discontinue Tenton if severe CNS adverse reactions develop.
Tenton may cause drowsiness; therefore, caution patients about engaging in activities requiring mental alertness and motor coordination, such as driving a car. Indomethacin may also cause headache. Headache which persists despite dosage reduction requires cessation of therapy with Tenton.
Ocular Effects
Corneal deposits and retinal disturbances, including those of the macula, have been observed in some patients who had received prolonged therapy with Tenton. Be alert to the possible association between the changes noted and Tenton. It is advisable to discontinue therapy if such changes are observed. Blurred vision may be a significant symptom and warrants a thorough ophthalmological examination. Since these changes may be asymptomatic, ophthalmologic examination at periodic intervals is desirable in patients receiving prolonged therapy. Tenton is not indicated for long-term treatment.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide) that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with Tenton and periodically during the course of ongoing therapy.
Cardiovascular Thrombotic Events
Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their health care provider immediately.
Gastrointestinal Bleeding, Ulceration, And Perforation
Hepatotoxicity
Inform patients of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, diarrhea, jaundice, right upper quadrant tenderness, and “flu-like” symptoms). If these occur, instruct patients to stop Tenton and seek immediate medical therapy.
Heart Failure And Edema
Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur.
Anaphylactic Reactions
Inform patients of the signs of an anaphylactic reaction (e.g., difficulty breathing, swelling of the face or throat). Instruct patients to seek immediate emergency help if these occur.
Serious Skin Reactions
Advise patients to stop Tenton immediately if they develop any type of rash and to contact their healthcare provider as soon as possible.
Female Fertility
Advise females of reproductive potential who desire pregnancy that NSAIDs, including Tenton, may be associated with a reversible delay in ovulation.
Fetal Toxicity
Inform pregnant women to avoid use of Tenton and other NSAIDs starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus.
Avoid Concomitant Use Of NSAIDs
Inform patients that the concomitant use of Tenton with other NSAIDs or salicylates (e.g., diflunisal, salsalate) is not recommended due to the increased risk of gastrointestinal toxicity, and little or no increase in efficacy. Alert patients that NSAIDs may be present in “over the counter” medications for treatment of colds, fever, or insomnia.
Use Of NSAIDs And Low-Dose Aspirin
Inform patients not to use low-dose aspirin concomitantly with Tenton until they talk to their healthcare provider.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Carcinogenesis
In an 81-week chronic oral toxicity study in the rat at doses up to 1 mg/kg/day (0.05 times the MRHD on a mg/m² basis), indomethacin had no tumorigenic effect. Indomethacin produced no neoplastic or hyperplastic changes related to treatment in carcinogenic studies in the rat (dosing period 73 to 110 weeks) and the mouse (dosing period 62 to 88 weeks) at doses up to 1.5 mg/kg/day (0.04 times [mice] and 0.07 times [rats] the MRHD on a mg/m² basis, respectively).
Mutagenesis
Indomethacin did not have any mutagenic effect in in vitro bacterial tests and a series of in vivo tests including the host-mediated assay, sex-linked recessive lethals in Drosophila, and the micronucleus test in mice.
Impairment Of Fertility
Indomethacin at dosage levels up to 0.5 mg/kg/day had no effect on fertility in mice in a two generation reproduction study (0.01 times the MRHD on a mg/m² basis) or a two litter reproduction study in rats (0.02 times the MRHD on a mg/m² basis).
Use In Specific Populations
Pregnancy
Risk Summary
Use of NSAIDs, including Tenton, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Avoid use of NSAIDs, including Tenton, in pregnant women starting at 30 weeks of gestation (third trimester).
There are no adequate and well-controlled studies of Tenton in pregnant women.
Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U.S. population, all clinically recognized pregnancies, regardless of drug exposure, have a background rate of 2-4% for major malformations, and 15-20% for pregnancy loss. In animal reproduction studies retarded fetal ossification was observed with administration of indomethacin to mice and rats during organogenesis at doses 0.1 and 0.2 times, respectively, the maximum recommended human dose (MRHD, 200 mg (40 mL)). In published studies in pregnant mice, indomethacin produced maternal toxicity and death, increased fetal resorptions, and fetal malformations at 0.1 times the MRHD. When rat and mice dams were dosed during the last three days of gestation, indomethacin produced neuronal necrosis in the offspring at 0.1 and 0.05 times the MRHD, respectively. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors such as indomethacin, resulted in increased pre- and post-implantation loss.
Clinical Considerations
Labor or Delivery
There are no studies on the effects of Tenton during labor or delivery. In animal studies, NSAIDs, including indomethacin, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.
Data
Animal data
Reproductive studies were conducted in mice and rats at dosages of 0.5, 1.0, 2.0, and 4.0 mg/kg/day. Except for retarded fetal ossification at 4 mg/kg/day (0.1 times [mice] and 0.2 times [rats] the MRHD on a mg/m² basis, respectively) considered secondary to the decreased average fetal weights, no increase in fetal malformations was observed as compared with control groups. Other studies in mice reported in the literature using higher doses (5 to 15 mg/kg/day, 0.1 to 0.4 times MRHD on a mg/m² basis) have described maternal toxicity and death, increased fetal resorptions, and fetal malformations.
In rats and mice, maternal indomethacin administration of 4.0 mg/kg/day (0.2 times and 0.1 times the MRHD on a mg/m² basis) during the last 3 days of gestation was associated with an increased incidence of neuronal necrosis in the diencephalon in the live-born fetuses however no increase in neuronal necrosis was observed at 2.0 mg/kg/day as compared to the control groups (0.1 times and 0.05 times the MRHD on a mg/m² basis). Administration of 0.5 or 4.0 mg/kg/day to offspring during the first 3 days of life did not cause an increase in neuronal necrosis at either dose level.
Lactation
Risk Summary
Based on available published clinical data, indomethacin may be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Tenton and any potential adverse effects on the breastfed infant from the Tenton or from the underlying maternal condition.
Data
In one study, levels of indomethacin in breast milk were below the sensitivity of the assay (<20 mcg/L) in 11 of 15 women using doses ranging from 75 mg orally to 300 mg rectally daily (0.94 to 4.29 mg/kg daily) in the postpartum period. Based on these levels, the average concentration present in breast milk was estimated to be 0.27% of the maternal weight-adjusted dose. In another study indomethacin levels were measured in breast milk of eight postpartum women using doses of 75 mg daily and the results were used to calculate an estimated infant daily dose. The estimated infant dose of indomethacin from breast milk was less than 30 mcg/day or 4.5 mcg/kg/day assuming breast milk intake of 150 mL/kg/day. This is 0.5% of the maternal weight-adjusted dosage or about 3% of the neonatal dose for treatment of patent ductusarteriosus.
Females And Males Of Reproductive Potential
Infertility
Females
Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Tenton, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin-mediated follicular rupture required for ovulation. Small studies in women treated with NSAIDs have also shown a reversible delay in ovulation. Consider withdrawal of NSAIDs, including Tenton, in women who have difficulties conceiving or who are undergoing investigation of infertility.
Pediatric Use
Safety and effectiveness in pediatric patients 14 years of age and younger has not been established.
Tenton should not be prescribed for pediatric patients 14 years of age and younger unless toxicity or lack of efficacy associated with other drugs warrants the risk.
In experience with more than 900 pediatric patients reported in the literature or to the manufacturer who were treated with Tenton Capsules, side effects in pediatric patients were comparable to those reported in adults. Experience in pediatric patients has been confined to the use of Tenton Capsules.
If a decision is made to use indomethacin for pediatric patients two years of age or older, such patients should be monitored closely and periodic assessment of liver function is recommended. There have been cases of hepatotoxicity reported in pediatric patients with juvenile rheumatoid arthritis, including fatalities. If indomethacin treatment is instituted, a suggested starting dose is 1-2 mg/kg/day given in divided doses. Maximum daily dosage should not exceed 3 mg/kg/day or 150-200 mg/day, whichever is less. Limited data are available to support the use of a maximum daily dosage of 4 mg/kg/day or 150- 200 mg/day, whichever is less. As symptoms subside, the total daily dosage should be reduced to the lowest level required to control symptoms, or the drug should be discontinued.
Geriatric Use
Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, gastrointestinal, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, start dosing at the low end of the dosing range, and monitor patients for adverse effects.
Indomethacin may cause confusion or rarely, psychosis ; physicians should remain alert to the possibility of such adverse effects in the elderly.
Indomethacin and its metabolites are known to be substantially excreted by the kidneys, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, use caution in this patient population, and it may be useful to monitor renal function.
Headache, sometimes accompanied by dizziness and light-headedness, may occur, usually early in treatment. Starting therapy with a low dosage and increasing it gradually will usually minimise the incidence of headache. These symptoms frequently disappear on continuing therapy or reducing the dosage, but if headache persists despite dosage reduction, 'Tenton' should be withdrawn. Patients should be warned that they may experience dizziness and, if they do, should not drive a car or undertake potentially dangerous activities needing alertness.
'Tenton' should be used cautiously in patients with a history of bronchial asthma and in patients with psychiatric disorders, epilepsy, or parkinsonism, as indomethacin may tend to aggravate these disorders.
NSAIDs should only be given with care to patients with a history of gastro-intestinal disease.
Gastro-intestinal disturbances may be minimised by giving 'Tenton' orally with food or an antacid. They usually disappear on reducing the dosage; if not, the risks of continuing therapy should be weighed against the possible benefits. If gastro-intestinal bleeding does occur, 'Tenton' should immediately be discontinued.
Single or multiple ulcerations, including perforation and haemorrhage of the oesophagus, stomach, duodenum or small or large intestine, have been reported to occur with 'Tenton'. Fatalities have been reported in some instances. Rarely, intestinal ulceration has been associated with stenosis and obstruction.
Gastro-intestinal bleeding without obvious ulcer formation and perforation of pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) have occurred. Increased abdominal pain in ulcerative colitis patients or the development of ulcerative colitis and regional ileitis have been reported to occur rarely.
Fluid retention and peripheral oedema have been observed in some patients taking 'Tenton'. 'Tenton' should therefore be used with caution in patients with cardiac dysfunction, hypertension or other conditions predisposing to fluid retention.
'Tenton' may mask the signs and symptoms of infection. 'Tenton' should be used with caution in patients with existing but controlled infection.
In patients with rheumatoid arthritis, eye changes may occur which may be related to the underlying disease or to the therapy. Therefore, in chronic rheumatoid disease, ophthalmological examinations at periodic intervals are recommended. Discontinue therapy if eye changes are observed.
Patients should be periodically observed to allow early detection of any unwanted effects on peripheral blood (anaemia), liver function, or gastro-intestinal tract.
'Tenton' can inhibit platelet aggregation. This effect usually disappears within 24 hours of discontinuing 'Tenton'. Bleeding time is prolonged (but within normal range) in normal adults. Because this effect may be exaggerated in patients with underlying haemostatic defects, 'Tenton' should be used cautiously in patients with coagulation defects.
As with other non-steroidal anti-inflammatory drugs, there have been reports of acute interstitial nephritis with haematuria, proteinuria, and occasionally nephrotic syndrome in patients receiving long-term administration of indomethacin.
In patients with reduced renal blood flow where renal prostaglandins play a major role in maintaining renal perfusion, administration of a non-steroidal anti-inflammatory agent may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with renal or hepatic dysfunction, diabetes mellitus, advanced age, extracellular volume depletion, congestive heart failure, sepsis, or concomitant use of any nephrotoxic drug. A non-steroidal anti-inflammatory drug should be given with caution and renal function should be monitored in any patient who may have reduced renal reserve. Discontinuation of non-steroidal anti-inflammatory therapy is usually followed by recovery to the pretreatment state.
Increases in plasma potassium concentration, including hyperkalaemia, have been reported, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninaemic-hypoaldosteronism state (see 4.5 'Interaction with other medicaments and other forms of interaction').
Since 'Tenton' is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored; a lower daily dosage should be used to avoid excessive drug accumulation.
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
Patients should be warned that they may experience dizziness, drowsiness, visual disturbances or headaches and if they do, should not drive or undertake activities requiring alertness.
- Blood and lymphatic disorders: blood dyscrasias (such as thrombocytopenia,
neutropenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia), bone marrow depression, petechiae, ecchymoses, purpura, and disseminated intravascular coagulation may occur infrequently. As some patients manifest anaemia secondary to obvious or occult gastro-intestinal bleeding, appropriate blood determinations are recommended. Epistaxis has been reported rarely.
- Hypersensitivity:Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis, (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, rhinitis or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
- Metabolic and nutrition disorders: Hyperglycaemia, glycosuria, hyperkalaemia has been reported rarely.
- Nervous system disorders: Visual disturbances, optic neuritis, tinnitus, headache, dizziness and lightheadedness are common side effects. Starting therapy with a low dose and increasing gradually minimises the incidence of headache. These symptoms frequently disappear on continued therapy or reducing the dosage, but if headache persists despite dosage reduction, Tenton should be withdrawn. Other CNS effects include reports of aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus or mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation , depression, vertigo, fatigue, malaise, dysarthria, syncope, coma, cerebral oedema, nervousness, confusion, anxiety and other psychiatric disturbances, depersonalisation, hallucinations, drowsiness, convulsions and aggravation of epilepsy and parkinsonism, peripheral neuropathy, paraesthesia, involuntary movements and insomnia. These effects are often transient and abate or disappear on reduced or stopping treatment. However, the severity of these may, on occasion, require cessation of therapy.
- Eye disorders: blurred vision, diplopia, optic neuritis and orbital and peri-orbital pain are seen infrequently. Corneal deposits and retinal or macular disturbances have been reported in some patients with rheumatoid arthritis on prolonged therapy with Tenton. Ophthalmic examinations are desirable in patients given prolonged treatment.
- Ear and labyrinth disorders: tinnitus or hearing disturbances (rarely deafness) have been reported.
- Cardiac disorders: There have been reports of hypotension, tachycardia, chest pain, arrhythmia, palpitations.
- Cardiovascular and cerebrovascular:
Oedema hypertension and cardiac failure have been reported in association with NSAID treatment.
- Vascular disorders: flushing has been reported rarely.
- Respiratory, thoracic and mediastinal disorders: pulmonary eosinophilia. There may be bronchospasm in patients with a history of bronchial asthma or other allergic disease.
- Gastrointestinal disorders: The most commonly-observed adverse events are gastrointestinal in nature. Anorexia, epigastric discomfort,ulceration at any point in the gastro-intestinal tract (even with resultant stenosis and obstruction), bleeding (even without obvious ulceration or from a diverticulum) and perforation of preexisting sigmoid lesions (such as diverticulum or carcinoma), increased abdominal pain or exacerbation of the condition in patients with ulcerative colitis or Crohns disease (or the development of this condition), intestinal strictures and regional ileitis have been rarely reported. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. If gastro-intestinal bleeding does occur treatment with Tenton should be discontinued. Gastro-intestinal disorders which occur can be reduced by giving Tenton with food, milk or antacids. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.
- Hepato-biliary disorders: cholestasis, borderline elevations of one or more liver tests may occur, and significant elevations of ALT (SGPT) or AST (SGOT) have been seen in less than 1% of patients receiving therapy with NSAIDs in controlled clinical trials. If abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations such as rash or eosinophilia occur, Tenton should be stopped. Abnormal liver function, hepatitis and jaundice.
- Skin and subcutaneous tissue disorders: pruritus, urticaria, angioneurotic oedema, angiitis, erythema nodosum, rash, photosensitivity, exfoliative dermatitis, bullous reactions including Stevens Johnson syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity, erythema multiforme, hair loss, sweating and exacerbation of psoriasis.
- Musculo-skeletal, connective tissue and bone disorders: muscle weakness and acceleration of cartilage degeneration.
- Renal and urinary disorders: haematuria, nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure, renal insufficiency, proteinuria have all been reported. In patients with renal, cardiac or hepatic impairment, caution is required since the use of non-steroidal anti-inflammatory drugs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored.
- Reproductive system and breast disorders: vaginal bleeding, breast changes (enlargement, tenderness, gynaecomastia)
- Clinical trial and epidemiological data suggest that the use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke).
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Cardiovascular Thrombotic Events
- GI Bleeding, Ulceration and Perforation
- Hepatotoxicity
- Hypertension
- Heart Failure and Edema
- Renal Toxicity and Hyperkalemia
- Anaphylactic Reactions
- Serious Skin Reactions
- Hematologic Toxicity
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In a gastroscopic study in 45 healthy subjects, the number of gastric mucosal abnormalities was significantly higher in the group receiving Tenton Capsules than in the group taking Tenton Suppositories or placebo.
In a double-blind comparative clinical study involving 175 patients with rheumatoid arthritis, however, the incidence of upper gastrointestinal adverse effects with Tenton Suppositories or Capsules was comparable. The incidence of lower gastrointestinal adverse effects was greater in the suppository group.
The adverse reactions for Tenton Capsules listed in the following table have been arranged into two groups: (1) incidence greater than 1%; and (2) incidence less than 1%. The incidence for group (1) was obtained from 33 double-blind controlled clinical trials reported in the literature (1,092 patients). The incidence for group (2) was based on reports in clinical trials, in the literature, and on voluntary reports since marketing. The probability of a causal relationship exists between Tenton and these adverse reactions, some of which have been reported only rarely.
The adverse reactions reported with Tenton Capsules may also occur with use of the suspension.
Table 1 : Summary of Adverse Reactions for Tenton Capsules
Incidence greater than 1 % | Incidence less than 1% | |
GASTROINTESTINAL | ||
nausea* with or without vomiting dyspepsia* (including indigestion, heartburn and epigastric pain) diarrhea abdominal distress or pain constipation | anorexia bloating (includes distension) flatulence peptic ulcer gastroenteritis rectal bleeding proctitis single or multiple ulcerations, including perforation and hemorrhage of the esophagus, stomach, duodenum or small and large intestines intestinal ulceration associated with stenosis and obstruction | gastrointestinal bleeding without obvious ulcer formation and perforation of preexisting sigmoid lesions (diverticulum, carcinoma, etc.) development of ulcerative colitis and regional ileitis ulcerative stomatitis toxic hepatitis and jaundice (some fatal cases have been reported) intestinal strictures (diaphragms) |
CENTRAL NERVOUS SYSTEM | ||
headache (11.7%) dizziness* vertigo somnolence depression and fatigue (including malaise and listlessness) | anxiety (includes nervousness) muscle weakness involuntary muscle movements insomnia muzziness psychic disturbances including psychotic episodes mental confusion drowsiness | light-headedness syncope paresthesia aggravation of epilepsy and parkinsonism depersonalization coma peripheral neuropathy convulsion dysarthria |
SPECIAL SENSES | ||
tinnitus | ocular — corneal deposits and retinal disturbances, including those of the macula, have been reported in some patients on prolonged therapy with Tenton | blurred vision diplopia hearing disturbances, deafness |
CARDIOVASCULAR | ||
None | hypertension hypotension tachycardia chest pain | congestive heart failure arrhythmia; palpitations |
METABOLIC | ||
None | edema weight gain fluid retention flushing or sweating | hyperglycemia glycosuria hyperkalemia |
INTEGUMENTARY | ||
none | pruritus rash; urticaria petechiae or ecchymosis | exfoliative dermatitis erythema nodosum loss of hair Stevens-Jonnson syndrome erythema multiforme toxic epidermal necrolysis |
HEMATOLOGIC | ||
None | leukopenia bone marrow depression anemia secondary to obvious or occult gastrointestinal bleeding | aplastic anemia hemolytic anemia agranulocytosis thrombocytopenic purpura disseminated intravascular coagulation |
HYPERSENSITIVITY | ||
None | acute anaphylaxis acute respiratory distress rapid fall in blood pressure resembling a shock-like state angioedema | dyspnea asthma purpura angiitis pulmonary edema fever |
GENITOURINARY | ||
None | hematuria vaginal bleeding proteinuria nephrotic syndrome interstitial nephritis | BUN elevation renal insufficiency, including renal failure |
MISCELLANEOUS | ||
None | epistaxis breast changes, including enlargement and tenderness, or gynecomastia | |
*Reactions occurring in 3% to 9% of patients treated with Tenton. (Those reactions occurring in less than 3% of the patients are unmarked.) |
Causal relationship unknown: Other reactions have been reported but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, the possibility cannot be excluded. Therefore, these observations are being listed to serve as alerting information to physicians:
Cardiovascular: Thrombophlebitis
Hematologic: Although there have been several reports of leukemia, the supporting information is weak
Genitourinary: Urinary frequency
A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group Aβ hemolytic streptococcus, has been described in persons treated with nonsteroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome
CNS reactions - headaches, dizziness, light-headedness, depression, vertigo, and fatigue (including malaise and listlessness). Reactions reported infrequently include mental confusion, anxiety, syncope, drowsiness, convulsions, coma, peripheral neuropathy, muscle weakness, involuntary muscle movements, insomnia, psychiatric disturbances such as hallucinations, depersonalisation; and, rarely, paraesthesia, dysarthria, aggravation of epilepsy and Parkinsonism. These are often transient and disappear frequently with continued treatment or with reduced dosage. However, occasionally, severe reactions require stopping therapy.
Gastro-intestinal - the more frequent reactions are nausea, anorexia, vomiting, epigastric distress, abdominal pain, constipation, and diarrhoea. Others which may develop are ulceration - single or multiple - of oesophagus, stomach, duodenum or small or large intestine, including perforation and haemorrhage with a few fatalities having been reported; gastro-intestinal tract bleeding without obvious ulcer formation; and increased abdominal pain when used in patients with pre-existing ulcerative colitis. Reactions occurring infrequently are stomatitis; gastritis; flatulence; bleeding from the sigmoid colon - occult or from a diverticulum - and perforation of pre-existing sigmoid lesions (diverticula, carcinoma). Rarely, intestinal strictures (diaphragms) and intestinal ulceration followed by stenosis and obstruction has been reported. With suppositories, tenesmus and irritation of the rectal mucosa have occasionally been reported. Pancreatitis has been reported with an unknown frequency. Other gastro-intestinal side effects which may or may not be caused by indomethacin include: ulcerative colitis and regional ileitis.
Hepatic - rarely, hepatitis and jaundice. (Some fatalities reported.)
Cardiovascular/Renal - oedema, increased blood pressure, tachycardia, chest pain, arrhythmia, palpitation, hypotension, congestive heart failure, blood urea elevation, and haematuria (all infrequent).
Dermatological/Hypersensitivity - pruritus, urticaria, angioneurotic oedema, angiitis, erythema nodosum, skin rash and photosensitivity, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, loss of hair, rapid fall in blood pressure resembling a shock-like state, acute anaphylaxis, acute respiratory distress including sudden dyspnoea, asthma and pulmonary oedema (all infrequent). Bronchospasm may be precipitated in patients suffering from, or with a history of, bronchial asthma or allergic disease.
Haematological - infrequently, blood dyscrasias may occur, including leucopenia, petechiae or ecchymosis, purpura, aplastic and haemolytic anaemia, agranulocytosis, bone-marrow depression, disseminated intravascular coagulation, and particularly thrombocytopenia. Because some patients may develop anaemia secondary to obvious or occult gastro-intestinal bleeding, appropriate blood determinations are recommended.
Ocular - infrequently, blurred vision, diplopia, and orbital and peri-orbital pain. Corneal deposits and retinal disturbances, including those of the macula, have been reported in patients with rheumatoid arthritis on prolonged therapy, but similar changes may also be expected in patients with rheumatoid arthritis who have not received indomethacin.
Aural - tinnitus, hearing disturbances (rarely deafness).
Genito-urinary - proteinuria, nephrotic syndrome, interstitial nephritis, and renal insufficiency including renal failure (all rare).
Miscellaneous - vaginal bleeding, hyperglycaemia, glycosuria, hyperkalaemia, flushing and sweating, epistaxis, breast changes including enlargement and tenderness, gynaecomastia, and ulcerative stomatitis (all rare).
Laboratory tests
Borderline elevations of one or more liver tests may occur, and significant elevations of ALT (SGPT) or AST (SGOT) have been seen in less than 1% of patients receiving therapy with non-steroidal anti-inflammatory drugs in controlled clinical trials. If abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations such as rash or eosinophilia occur, 'Tenton' should be stopped.
False-negative results in the dexamethasone suppression test (DST) in patients being treated with 'Tenton' have been reported. Thus, results of this test should be used with caution in these patients.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme.
Website: www.mhra.gov.uk/yellowcard
CODE ATC: M01A B01
Tenton est un agent anti-inflammatoire non stéroïdien aux propriétés analgésiques et antipytrétiques.
Les propriétés analgésiques ont été attribuées à la fois à l'effet central et périphérique, qui sont distinctes de son activité anti-inflammatoire.
L'indométhacine a des effets anti-inflammatoires, antipyrétiques et analgésiques, c'est un inhibiteur de la prostaglandine synthétase.
Absorption: Tenton est facilement absorbé par le tractus gastro-intestinal; les concentrations plasmatiques maximales sont atteintes environ 0,5 à 2 heures après une dose.
Distribution: Plus de 90% sont liés aux protéines plasmatiques. Il est distribué dans le liquide synovial, le SNC et le placenta. De faibles concentrations ont été trouvées dans le mik du sein.
Métabolisme: Il est métabolisé dans le foie principalement par déméthylation et désacétylation, il subit également une glucuronidation et une circulation entérohépatique. La demi-vie se situe entre 3 et 11 heures.
Élimination: Principalement excrété dans l'urine, environ 60%, le pH de l'urine peut affecter cette quantité. Des quantités moindres dans les fèces. Le tenton est également excrété dans le lait en petites quantités.
Absorption
Après des doses orales uniques de capsules de Tenton 25 mg ou 50 mg, l'indométhacine est facilement absorbée, atteignant des concentrations plasmatiques maximales d'environ 1 et 2 mcg / ml, respectivement, à environ 2 heures. Les capsules de Tenton administrées par voie orale sont pratiquement 100% biodisponibles, avec 90% de la dose absorbée dans les 4 heures. Une dose unique de 50 mg de suspension buvable de Tenton s'est avérée bioéquivalente à une capsule de Tenton de 50 mg lorsque chacune a été administrée avec de la nourriture. Avec un schéma thérapeutique typique de 25 ou 50 mg trois fois par jour, les concentrations plasmatiques à l'état d'équilibre de l'indométhacine sont en moyenne 1,4 fois celles qui suivent la première dose.
Distribution
L'indométhacine est fortement liée aux protéines plasmatiques (environ 99%) sur la plage attendue de concentrations plasmatiques thérapeutiques. L'indométhacine a traversé la barrière hémato-encéphalique et le placenta et apparaît dans le lait maternel.
Élimination
Métabolisme
L'indométhacine existe dans le plasma en tant que médicament parent et ses métabolites desméthyl, desbenzoyl et desméthyldesbenzoyle, le tout sous forme non conjuguée. Une formation appréciable de conjugués glucuronides de chaque métabolite et d'indométhacine se forme.
Excrétion
L'indométhacine est éliminée par excrétion rénale, métabolisme et excrétion biliaire. L'indométhacine subit une circulation entérohépatique appréciable. Environ 60% d'une dose orale est récupérée dans l'urine sous forme de médicament et de métabolites (26% sous forme d'indométhacine et de glucuronide), et 33% est récupérée dans les fèces (1,5% sous forme d'indométhacine). La demi-vie moyenne de l'indométhacine est estimée à environ 4,5 heures.
L'indométhacine est rapidement et presque complètement absorbée par administration orale, et les concentrations plasmatiques maximales sont atteintes en ½ à 2 heures. L'absorption est ralentie mais reste pratiquement complète lorsqu'elle est prise avec de la nourriture. Environ 90% sont liés aux protéines plasmatiques. Il semble subir un cycle entérohépatique. Il est métabolisé en partie par O-déméthylation, en partie par N-désacylation, et le médicament et les métabolites inchangés sont en partie conjugués à l'acide glucoronique, chez l'homme, il est excrété sous forme inchangée et sous forme de métabolites dans l'urine et les fèces.
Sans objet.
Données administrativesLes capsules «Tenton» doivent toujours être prises avec de la nourriture ou un antiacide.
However, we will provide data for each active ingredient